Growth of Aspergillus fumigatus in Biofilms in Comparison to Candida albicans

Biofilm formation during infections with the opportunistic pathogen Aspergillus fumigatus can be very problematic in clinical settings, since it provides the fungal cells with a protective environment. Resistance against drug treatments, immune recognition as well as adaptation to the host environment allows fungal survival in the host. The exact molecular mechanisms behind most processes in the formation of biofilms are unclear. In general, the formation of biofilms can be categorized roughly in a few stages; adhesion, conidial germination and development of hyphae, biofilm maturation and cell dispersion. Fungi in biofilms can adapt to the in-host environment. These adaptations can occur on a level of phenotypic plasticity via gene regulation. However, also more substantial genetic changes of the genome can result in increased resistance and adaptation in the host, enhancing the survival chances of fungi in biofilms. Most research has focused on the development of biofilms. However, to tackle developing microbial resistance and adaptation in biofilms, more insight in mechanisms behind genetic adaptations is required to predict which defense mechanisms can be expected. This can be helpful in the development of novel and more targeted antifungal treatments to combat fungal infections.

Extracellular RNA as a potential activator of Neutrophil Extracellular Traps by Candida albicans biofilm

Neutrophils represent the first line of innate host defense. The ability to inhibit the development of infections is associated with the involvement of several fighting strategies. The still poorly understood mechanism is netosis, involving the release of Extracellular Neutrophil Traps (NETs). NETs are complexes of chromosomal DNA and granule content. Such a web-like structure inhibits the spread of invaders. Netosis plays a significant role in combating Candida albicans infections. It has been shown that several factors, composing C. albicans cell surface mediate NETs production. However, the development of difficult to eradicate fungal infection is associated with the formation of the biofilm structure, which partially protects the pathogen cells from contact with the host’s immune system. One of the reasons for the creation of a such protective environment is the production of the extracellular matrix (ECM). The major components of the C. albicans ECM layer are lipids, proteins, carbohydrates but also extracellular nucleic acids, among which we observed a significant RNA content. Considering that the ECM consisting of RNA molecules is one of the first lines of contact between biofilms and neutrophils, our current studies aimed to assess the potential role of extracellular RNA in the triggering of the netosis process by human neutrophils in vitro. We showed that RNA purified from C. albicans biofilm structure and the whole cells have the capability to induction of ROS-dependent netosis pathway. Additionally, cell migration analysis indicate that RNA molecules may also be an effective chemotactic agent. This work was supported by NCN (2019/33/B/NZ6/02284).

Exosomes as Powerful Engines in Cancer: Isolation, Characterization and Detection Techniques

Exosomes, powerful extracellular nanovesicles released from almost all types of living cells, are considered the communication engines (messengers) that control and reprogram physiological pathways inside target cells within a community or between different communities. The cell-like structure of these extracellular vesicles provides a protective environment for their proteins and DNA/RNA cargos, which serve as biomarkers for many malicious diseases, including infectious diseases and cancers. Cancer-derived exosomes control cancer metastasis, prognosis, and development. In addition to the unique structure of exosomes, their nanometer size and tendency of interacting with cells makes them a viable novel drug delivery solution. In recent years, numerous research efforts have been made to quantify and characterize disease-derived exosomes for diagnosis, monitoring, and therapeutic purposes. This review aims to (1) relate exosome biomarkers to their origins, (2) focus on current isolation and detection methods, (3) discuss and evaluate the proposed technologies deriving from exosome research for cancer treatment, and (4) form a conclusion about the prospects of the current exosome research.

COVID-19 Experience Transforming the Protective Environment of Office Buildings and Spaces

The COVID-19 pandemic has affected human life in every possible way and, alongside this, the need has been felt that office buildings and workplaces must have protective and preventive layers against COVID-19 transmission so that a smooth transition from ‘work from home’ to ‘work from office’ is possible. However, a comprehensive understanding of how the protective environment can be built around office buildings and workspaces, based on the year-long experience of living with COVID-19, is largely absent. The present study reviews international agency regulation, country regulation, updated journal articles, etc., to critically understand lessons learned from the COVID-19 pandemic and evaluate the expected changes in sustainability requirements of office buildings and workplaces. The built environment, control environment, and regulatory environment around office buildings and workplaces have been put under test on safety grounds during the pandemic. Workers switched over to safely work from home. Our findings bring out the changes required to be affected in the three broad environmental dimensions to limit their vulnerability status experienced during the pandemic. Office building designs should be fundamentally oriented to provide certain safety protective measures to the workers, such as touch-free technologies, open working layouts, and workplace flexibilities to diminish the probability of getting infected. Engineering and administrative control mechanisms should work in a complementary way to eliminate the risk of disease spread. Country regulation, agency regulations, and operational guidelines need to bring behavioral changes required to protect workers from the COVID-19 pandemic.

Rift Valley Fever Virus Propagates in Human Villous Trophoblast Cell Lines and Induces Cytokine mRNA Responses Known to Provoke Miscarriage

The mosquito-borne Rift Valley fever (RVF) is a prioritised disease that has been listed by the World Health Organization for urgent research and development of counteraction. Rift Valley fever virus (RVFV) can cause a cytopathogenic effect in the infected cell and induce hyperimmune responses that contribute to pathogenesis. In livestock, the consequences of RVFV infection vary from mild symptoms to abortion. In humans, 1–3% of patients with RVFV infection develop severe disease, manifested as, for example, haemorrhagic fever, encephalitis or blindness. RVFV infection has also been associated with miscarriage in humans. During pregnancy, there should be a balance between pro-inflammatory and anti-inflammatory mediators to create a protective environment for the placenta and foetus. Many viruses are capable of penetrating that protective environment and infecting the foetal–maternal unit, possibly via the trophoblasts in the placenta, with potentially severe consequences. Whether it is the viral infection per se, the immune response, or both that contribute to the pathogenesis of miscarriage remains unknown. To investigate how RVFV could contribute to pathogenesis during pregnancy, we infected two human trophoblast cell lines, A3 and Jar, representing normal and transformed human villous trophoblasts, respectively. They were infected with two RVFV variants (wild-type RVFV and RVFV with a deleted NSs protein), and the infection kinetics and 15 different cytokines were analysed. The trophoblast cell lines were infected by both RVFV variants and infection caused upregulation of messenger RNA (mRNA) expression for interferon (IFN) types I–III and inflammatory cytokines, combined with cell line-specific mRNA expression of transforming growth factor (TGF)-β1 and interleukin (IL)-10. When comparing the two RVFV variants, we found that infection with RVFV lacking NSs function caused a hyper-IFN response and inflammatory response, while the wild-type RVFV suppressed the IFN I and inflammatory response. The induction of certain cytokines by RVFV infection could potentially lead to teratogenic effects that disrupt foetal and placental developmental pathways, leading to birth defects and other pregnancy complications, such as miscarriage.

Urinary Extracellular Vesicles contain simplified transcriptomes enriched in circular & long noncoding RNAs with functional significance in prostate cancer

Long noncoding (lnc)RNAs modulate gene expression alongside presenting unexpected source of neoantigens. Despite their immense interest, their ability to be transferred and control adjacent cells is unknown. Extracellular Vesicles (EVs) offer a protective environment for nucleic acids, with pro and anti-tumorigenic functions by controlling the immune response. In contrast to extracellular non-vesicular RNA, few studies have addressed the full RNA content within human fluids’ EVs and none have compared them with their tissue of origin. Here, we performed Total RNA-Sequencing on 6 Formaldehyde-Fixed-Parafilm-Embedded (FFPE) prostate cancer (PCa) tumor tissues and their paired urinary (u)EVs to provide the first whole transcriptome comparison from the same patients. UEVs contain simplified transcriptome with intron-free cytoplasmic transcripts and specific lnc/circular (circ)RNAs, strikingly common to all patients. Our full cellular and EVs transcriptome comparison within 3 common PCa cell lines identified a set of overlapping 14 uEV-circRNAs characterized as essential for prostate cell proliferation in vitro and 15 uEV-lncRNAs that we predicted to encode 768 high-affinity neoantigens. Our dual analysis of EVs-lnc/circRNAs both in urines’ and in vitro’s EVs provides a fundamental resource for future uEV-lnc/circRNAs phenotypic characterization involved in PCa.

Prostate cancer urinary Extracellular Vesicles are enriched in cytoplasmic intron-free mRNAs and circular/long noncoding RNAs with functional significance

Long noncoding (lnc)RNAs modulate gene expression alongside presenting unexpected source of neoantigens. Despite their immense interest, their ability to be transferred and control adjacent cells is unknown. Extracellular Vesicles (EVs) offer a protective environment for nucleic acids, with pro and anti-tumorigenic functions by controlling the immune response. In contrast to extracellular non-vesicular RNA, few studies have addressed the full RNA content within human fluids’ EVs and none have compared them with their tissue of origin. Here, we performed Total RNA-Sequencing on 6 Formaldehyde-Fixed-Parafilm-Embedded (FFPE) prostate cancer (PCa) tumor tissues and their paired urinary (u)EVs to provide the first whole transcriptome comparison from the same patients. UEVs contain simplified transcriptome with intron-free cytoplasmic transcripts and specific lnc/circular (circ)RNAs, strikingly common to all patients. Our full cellular and EVs transcriptome comparison within 3 common PCa cell lines identified a set of overlapping 14 uEV-circRNAs characterized as essential for prostate cell proliferation in vitro and 15 uEV-lncRNAs that we predicted to encode 768 high-affinity neoantigens. Our dual analysis of EVs-lnc/circRNAs both in urines’ and in vitro’s EVs provides a fundamental resource for future uEV-lnc/circRNAs phenotypic characterization involved in PCa.

Balancing the Books and Staging Operas under Duress: Bolshoi Theater Management, Wartime Economy and State Sponsorship in 1941–1945

The article examines the financial history of the Bolshoi within USSR’s mobilized wartime cultural industry as an example of a cultural institution highly placed in the Stalinist establishment and symbolic canon. It explores the income-outcome flows, personnel management, the impact of evacuation, notably on Bolshoi’s hard capital, and relations with supervising authorities. The theater’s perceived importance within the war effort conditioned unshakable financial support, a non-market protective environment, and lenient administrative treatment, contrasting with logistical and personnel challenges which the house only partly mastered. This relative stability stands in contrast with the absence of strong leadership, as the director’s position was kept vacant in stark difference to most European opera theaters. The shock of 1941–1942 was absorbed with internal adjustment measures and external subventions, and the Bolshoi’s budgets swelled towards the end of the war, indicating inflation and the house’s “most-favored-opera status”. The stable and conservative management still showed shortcomings, which the state chose not to punish. The opera’s symbolic and prestige capital trumped quantitative efficiency, creating a haven in the war economy.

Frog nest foams exhibit pharmaceutical foam-like properties

Foams have frequently been used as systems for the delivery of cosmetic and therapeutic molecules; however, there is high variability in the foamability and long-term stability of synthetic foams. The development of pharmaceutical foams that exhibit desirable foaming properties, delivering appropriate amounts of the active pharmaceutical ingredient (API) and that have excellent biocompatibility is of great interest. The production of stable foams is rare in the natural world; however, certain species of frogs have adopted foam production as a means of providing a protective environment for their eggs and larvae from predators and parasites, to prevent desiccation, to control gaseous exchange, to buffer temperature extremes, and to reduce UV damage. These foams show great stability (up to 10 days in tropical environments) and are highly biocompatible due to the sensitive nature of amphibian skin. This work demonstrates for the first time that nests of the túngara frog ( Engystomops pustulosus ) are stable ex situ with useful physiochemical and biocompatible properties and are capable of encapsulating a range of compounds, including antibiotics. These protein foam mixtures share some properties with pharmaceutical foams and may find utility in a range of pharmaceutical applications such as topical drug delivery systems.

Stem Cells: Innovative Therapeutic Options for Neurodegenerative Diseases?

Neurodegenerative diseases are characterized by the progressive loss of structure and/or function of both neurons and glial cells, leading to different degrees of pathology and loss of cognition. The hypothesis of circuit reconstruction in the damaged brain via direct cell replacement has been pursued extensively so far. In this context, stem cells represent a useful option since they provide tissue restoration through the substitution of damaged neuronal cells with exogenous stem cells and create a neuro-protective environment through the release of bioactive molecules for healthy neurons, as well. These peculiar properties of stem cells are opening to potential therapeutic strategies for the treatment of severe neurodegenerative disorders, for which the absence of effective treatment options leads to an increasingly socio-economic burden. Currently, the introduction of new technologies in the field of stem cells and the implementation of alternative cell tissues sources are pointing to exciting frontiers in this area of research. Here, we provide an update of the current knowledge about source and administration routes of stem cells, and review light and shadows of cells replacement therapy for the treatment of the three main neurodegenerative disorders (Amyotrophic lateral sclerosis, Parkinson’s, and Alzheimer’s disease).